The TrkB-Shc site signals neuronal survival and local axon growth via MEK and PI3-kinase

To determine how signals emanating from Trk transmit neurotrophin actions in primary neurons, we tested the ability of TrkB mutated at defined effector binding sites to promote sympathetic neuron survival or local axon growth. TrkB stimulated signaling proteins and induced survival and growth in a manner similar to TrkA. TrkB mutated at the Shc binding site supported survival and growth poorly relative to wild-type TrkB, whereas TrkB mutated at the PLC-gamma 1 binding site supported growth and survival well. TrkB-mediated neuronal survival was dependent on PI3-kinase and to a lesser extent MEK activity, while growth depended upon both MEK and PI3-kinase activities. These results indicate that the TrkB-Shc site mediates both neuronal survival and axonal outgrowth by activating the PI3-kinase and MEK signaling pathways.